Mitochondrial respiration and metabolism play an important role in the occurrence and development of colorectal cancer (CRC). In this study, we identified a functional pool of SLIT-ROBO Rho GTPase-activating protein 2 (SRGAP2) in the mitochondria of CRC cells as an important regulator of CRC chemosensitivity. We found that SRGAP2 levels were increased in CRC cells in comparison to normal colorectal cells. Loss of mitochondrial SRGAP2 led to significant decrease in mitochondrial respiration and strongly sensitized the CRC cells to chemotherapy drugs. Mechanistically, SRGAP2 physically interacts with mitochondrial complex I and positively modulates its activity. In particular, chemosensitization upon SRGAP2 loss was phenocopied by the treatment of complex I inhibitor. Thus, our results demonstrate that SRGAP2 functions as a key regulator of CRC chemosensitivity, identifying SRGAP2 as a promising therapeutic target to enhance the efficacy of chemotherapy in CRC.
基金：
Key Research and Development Project of Chuzhou [2020ZN007]
第一作者机构：[1]Anhui Med Univ, Peoples Hosp Chuzhou 1, Chuzhou Hosp, Dept Gastrointestinal Surg, Chuzhou, Peoples R China
共同第一作者：
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推荐引用方式(GB/T 7714)：
Tang Yongqin,Liu Guijun,Jia Yanhan,et al.SRGAP2 controls colorectal cancer chemosensitivity via regulation of mitochondrial complex I activity[J].HUMAN CELL.2022,35(6):1928-1938.doi:10.1007/s13577-022-00781-7.
APA：
Tang, Yongqin,Liu, Guijun,Jia, Yanhan&Sun, Tao.(2022).SRGAP2 controls colorectal cancer chemosensitivity via regulation of mitochondrial complex I activity.HUMAN CELL,35,(6)
MLA：
Tang, Yongqin,et al."SRGAP2 controls colorectal cancer chemosensitivity via regulation of mitochondrial complex I activity".HUMAN CELL 35..6(2022):1928-1938
